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2.
Proc Natl Acad Sci U S A ; 120(10): e2219388120, 2023 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-36848559

RESUMEN

The soluble fraction of atmospheric transition metals is particularly associated with health effects such as reactive oxygen species compared to total metals. However, direct measurements of the soluble fraction are restricted to sampling and detection units in sequence burdened with a compromise between time resolution and system bulkiness. Here, we propose the concept of aerosol-into-liquid capture and detection, which allowed one-step particle capture and detection via the Janus-membrane electrode at the gas-liquid interface, enabling active enrichment and enhanced mass transport of metal ions. The integrated aerodynamic/electrochemical system was capable of capturing airborne particles with a cutoff size down to 50 nm and detecting Pb(II) with a limit of detection of 95.7 ng. The proposed concept can pave the way for cost-effective and miniaturized systems, for the capture and detection of airborne soluble metals in air quality monitoring, especially for abrupt air pollution events with high airborne metal concentrations (e.g., wildfires and fireworks).

3.
BMC Bioinformatics ; 25(1): 282, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39198740

RESUMEN

BACKGROUND: Thermostability is a fundamental property of proteins to maintain their biological functions. Predicting protein stability changes upon mutation is important for our understanding protein structure-function relationship, and is also of great interest in protein engineering and pharmaceutical design. RESULTS: Here we present mutDDG-SSM, a deep learning-based framework that uses the geometric representations encoded in protein structure to predict the mutation-induced protein stability changes. mutDDG-SSM consists of two parts: a graph attention network-based protein structural feature extractor that is trained with a self-supervised learning scheme using large-scale high-resolution protein structures, and an eXtreme Gradient Boosting model-based stability change predictor with an advantage of alleviating overfitting problem. The performance of mutDDG-SSM was tested on several widely-used independent datasets. Then, myoglobin and p53 were used as case studies to illustrate the effectiveness of the model in predicting protein stability changes upon mutations. Our results show that mutDDG-SSM achieved high performance in estimating the effects of mutations on protein stability. In addition, mutDDG-SSM exhibited good unbiasedness, where the prediction accuracy on the inverse mutations is as well as that on the direct mutations. CONCLUSION: Meaningful features can be extracted from our pre-trained model to build downstream tasks and our model may serve as a valuable tool for protein engineering and drug design.


Asunto(s)
Mutación , Estabilidad Proteica , Proteínas , Proteínas/química , Proteínas/genética , Proteínas/metabolismo , Mioglobina/química , Mioglobina/genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/química , Proteína p53 Supresora de Tumor/metabolismo , Biología Computacional/métodos , Aprendizaje Profundo , Aprendizaje Automático Supervisado , Bases de Datos de Proteínas , Conformación Proteica
4.
Small ; 20(31): e2312288, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38431966

RESUMEN

The development of capable of simultaneously modulating the sluggish electrochemical kinetics, shuttle effect, and lithium dendrite growth is a promising strategy for the commercialization of lithium-sulfur batteries. Consequently, an elaborate preparation method is employed to create a host material consisting of multi-channel carbon microspheres (MCM) containing highly dispersed heterostructure Fe3O4-FeTe nanoparticles. The Fe3O4-FeTe@MCM exhibits a spontaneous built-in electric field (BIEF) and possesses both lithophilic and sulfophilic sites, rendering it an appropriate host material for both positive and negative electrodes. Experimental and theoretical results reveal that the existence of spontaneous BIEF leads to interfacial charge redistribution, resulting in moderate polysulfide adsorption which facilitates the transfer of polysulfides and diffusion of electrons at heterogeneous interfaces. Furthermore, the reduced conversion energy barriers enhanced the catalytic activity of Fe3O4-FeTe@MCM for expediting the bidirectional sulfur conversion. Moreover, regulated Li deposition behavior is realized because of its high conductivity and remarkable lithiophilicity. Consequently, the battery exhibited long-term stability for 500 cycles with 0.06% capacity decay per cycle at 5 C, and a large areal capacity of 7.3 mAh cm-2 (sulfur loading: 9.73 mg cm-2) at 0.1 C. This study provides a novel strategy for the rational fabrication of heterostructure hosts for practical Li-S batteries.

5.
Plant Physiol ; 194(1): 391-407, 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-37738410

RESUMEN

Exposure of dark-grown etiolated seedlings to light triggers the transition from skotomorphogenesis/etiolation to photomorphogenesis/de-etiolation. In the life cycle of plants, de-etiolation is essential for seedling development and plant survival. The mobilization of soluble sugars (glucose [Glc], sucrose, and fructose) derived from stored carbohydrates and lipids to target organs, including cotyledons, hypocotyls, and radicles, underpins de-etiolation. Therefore, dynamic carbohydrate biochemistry is a key feature of this phase transition. However, the molecular mechanisms coordinating carbohydrate status with the cellular machinery orchestrating de-etiolation remain largely opaque. Here, we show that the Glc sensor HEXOKINASE 1 (HXK1) interacts with GROWTH REGULATOR FACTOR5 (GRF5), a transcriptional activator and key plant growth regulator, in Arabidopsis (Arabidopsis thaliana). Subsequently, GRF5 directly binds to the promoter of phytochrome A (phyA), encoding a far-red light (FR) sensor/cotyledon greening inhibitor. We demonstrate that the status of Glc within dark-grown etiolated cotyledons determines the de-etiolation of seedlings when exposed to light irradiation by the HXK1-GRF5-phyA molecular module. Thus, following seed germination, accumulating Glc within dark-grown etiolated cotyledons stimulates a HXK1-dependent increase of GRF5 and an associated decrease of phyA, triggering the perception, amplification, and relay of HXK1-dependent Glc signaling, thereby facilitating the de-etiolation of seedlings following light irradiation. Our findings, therefore, establish how cotyledon carbohydrate signaling under subterranean darkness is sensed, amplified, and relayed, determining the phase transition from skotomorphogenesis to photomorphogenesis on exposure to light irradiation.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Plantones/metabolismo , Cotiledón/metabolismo , Etiolado , Glucosa/metabolismo , Luz , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fitocromo A/metabolismo , Regulación de la Expresión Génica de las Plantas
6.
Plant Cell Environ ; 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39403855

RESUMEN

Plant growth and development are governed via signal networks that connect inputs from nutrient status, hormone signals, and environmental cues. Substantial researches have indicated a pivotal role of sugars as signalling molecules in plants that integrate external environmental cues and other nutrients with intrinsic developmental programmes regulated via multiple plant hormones. Therefore, plant growth and development are controlled through complication signalling networks. However, in many studies, to obtain more obviously experimental findings, excess concentrations of applied exogenous sugars have aggravated the complexity of this signalling networks. Once researchers underestimate this complexity, a series of contradictory or contrasting findings will be generated. More importantly, in terms of these contradictory findings, more contradictory study outcomings are derived. In this review, we carefully analyze some reports, and find that these reports have confused or neglected that the sugar-antagonism of ethylene signalling is specific or conditional. As a result, many contradictory conclusions are generated, which will in turn misdirect the scientific community.

7.
Opt Express ; 32(10): 16722-16731, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38858871

RESUMEN

This work reports the nonlinear dynamics of a mid-infrared interband cascade laser (ICL) subject to optical injection. It is shown that the stable locking regime is asymmetric and broadens with increasing injection strength. Outside the locking regime, the ICL mostly produces period-one oscillations. However, three categories of periodic pulse oscillations are observed in the vicinity of the Hopf bifurcation and the saddle-node bifurcation. In particular, it is found that the ICL generates broadband chaos at a near-threshold pump current, and the chaos bandwidth is over 300 MHz.

8.
Opt Lett ; 49(11): 3142-3145, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824348

RESUMEN

Near-infrared semiconductor lasers subject to optical feedback usually produce chaos with a broad bandwidth of a few GHz. However, the reported mid-infrared interband cascade lasers (ICLs) only show chaos with a limited bandwidth below 1 GHz. Here we show that an ICL with optical feedback is able to generate broadband chaos as well. The mid-infrared chaos exhibits a remarkable bandwidth of about 6 GHz, which is comparable to that of the near-infrared counterpart. In addition, the spectral coverage in the electrical domain reaches as high as 17.7 GHz. It is found that the chaos bandwidth generally broadens with increasing feedback ratio and/or increasing pump current of the laser, while it is insensitive to the feedback length.

9.
Chem Res Toxicol ; 37(6): 957-967, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38771128

RESUMEN

Lung cancer is the main cause of cancer deaths around the world. Nitrosamine 4-(methyl nitrosamine)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific carcinogen of lung cancer. Abundant evidence implicates long noncoding RNAs (lncRNAs) in tumorigenesis. Yet, the effects and mechanisms of lncRNAs in NNK-induced carcinogenesis are still unclear. In this study, we discovered that NNK-induced transformed Beas-2B cells (Beas-2B-NNK) showed increased cell migration and proliferation while decreasing rates of apoptosis. RNA sequencing and differentially expressed lncRNAs analyses showed that lncRNA PSMB8-AS1 was obviously upregulated. Interestingly, silencing the lncRNA PSMB8-AS1 in Beas-2B-NNK cells reduced cell proliferation and migration and produced cell cycle arrest in the G2/M phase along with a decrease in CDK1 expression. Conclusively, our results demonstrate that lncRNA PSMB8-AS1 could promote the malignant characteristics of Beas-2B-NNK cells by regulating CDK1 and affecting the cell cycle, suggesting that it may supply a new prospective epigenetic mechanism for lung cancer.


Asunto(s)
Bronquios , Carcinógenos , Ciclo Celular , Células Epiteliales , Nicotiana , ARN Largo no Codificante , Humanos , Bronquios/citología , Bronquios/patología , Bronquios/efectos de los fármacos , Carcinógenos/toxicidad , Ciclo Celular/efectos de los fármacos , Línea Celular , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Nicotiana/química , Nitrosaminas/toxicidad , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
10.
Langmuir ; 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39475720

RESUMEN

Hybrid-wetting surfaces with hydrophilic spots reduced from the micrometer to nanometer scale have been confirmed to enhance vapor nucleation while simultaneously minimizing droplet pinning. Given that surface topography also plays a critical role in influencing nucleation characteristics, the effect of competition between intrinsic wettability and topography on nucleation remains unclear when both surface topography and hydrophilic regions approach the critical nucleation size. This work investigated vapor nucleation on two types of hybrid-wetting nanoconvex surfaces. On random hybrid-wetting convex surfaces, the most negative potential energy sites were located at the sides of the convex structures, leading vapor to preferentially nucleate at these locations, consistent with observations on homogeneous surfaces. Despite similar average potential energy values across the surface, wettability variations in hydrophilic and hydrophobic atoms significantly alter the surface energy distribution. As the wettability difference between hydrophilic and hydrophobic atoms increases, stronger hydrophilic atoms generate relatively higher local energy regions, promoting vapor rapid nucleation. The edge effect still exists at a hydrophilic atom ratio of 10%, and competition among hydrophilic spots impedes vapor nucleation and growth. However, when the ratio increases to 40%, the increased surface average potential energy promotes the probability of vapor contacting the surface, leading to rapid vapor nucleation on the sides of the convex structures. In addition, surface potential energy analysis and the Monte Carlo method revealed that nucleation locations on nanoconvex surfaces are governed by the competition between intrinsic wettability and topography. When the magnitude of the potential energy generated by the hydrophilic atoms exceeds that from the topography, stronger solid-liquid interactions at the top of the convex structure increase the likelihood of vapor contacting the surface, resulting in nucleation at the top. Conversely, when the magnitude of the potential energy generated by hydrophilic atoms is lower than that from topography, nucleation preferentially still occurs on the sides.

11.
Pharmacol Res ; 200: 107060, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38185210

RESUMEN

OBJECTIVE: To assess the efficacy and safety of FDA-approved KRASG12C inhibitors in patients with KRASG12C-mutated solid tumors. METHODS: We searched PubMed, EMBASE, Cochrane Library, and major international conferences for clinical trials published in English up to March 6, 2023. Clinical trials investigating sotorasib or adagrasib and reporting the clinical outcomes of the objective response rate (ORR), disease control rate (DCR), or incidence rate of grade ≥ 3 adverse events (AEs) were eligible. The primary endpoint was the ORR. Secondary endpoints included the DCR, incidence rate of grade ≥ 3 AEs, and odds ratio (OR) of the ORR between patients with or without co-mutation. The Random-effects model was applied for the outcomes of interest. RESULTS: 18 studies with 1224 patients were included in this meta-analysis. The pooled ORR, DCR, and incidence rate of grade ≥ 3 AEs were 31 % (95 % CI, 25-37 %), 86 % (95 % CI, 82-89 %), and 29 % (95 % CI, 23-36 %), respectively. KRASG12C-mutated NSCLC patients with a co-mutation of KEAP1 exhibited a worse ORR than those with wild-type KEAP1 (OR: 0.35, 95 % CI: 0.16-0.77). CONCLUSIONS: This study provided a comprehensive understanding of the efficacy and safety of KRASG12C inhibitors in treating solid tumors and identified KEAP1 mutation as a potential predictive biomarker of inferior response in patients treated with KRASG12C inhibitors. These findings may assist in the design of future clinical trials for identifying populations that may benefit from KRASG12C inhibitor treatment.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Proteína 1 Asociada A ECH Tipo Kelch , Proteínas Proto-Oncogénicas p21(ras) , Factor 2 Relacionado con NF-E2 , Mutación
12.
Value Health ; 27(8): 1108-1120, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38677363

RESUMEN

OBJECTIVES: To develop the EQ-5D-5L (5L) population norms for China and to assess the relationship between various factors and 5L data. METHODS: This study used data derived from the Psychology and Behavior Investigation of Chinese Residents, a national sample survey of 21 909 representative participants aged 12 years and above. Participants' health-related quality of life (HRQoL) was measured by the 5L. Their socioeconomic characteristics, behavioral factors, and health conditions were also obtained from the survey. Norm scores were generated and compared for different socioeconomic variables. Multiple linear and logistic regressions were used to assess the relationships of the 3 kinds of variables with the 5L utility, visual analog scale (VAS) scores and 5L health problems. RESULTS: The mean (SD) age of participants was 39.4 (18.9) years, and 50.0% of them were female. The mean (SD) utility and VAS scores were 0.940 (0.138) and 73.4 (21.6), respectively. Participants reported considerably more problems in anxiety/depression (26.2%) and pain/discomfort (22.2%) dimensions. The gender difference in HRQoL is attenuated. The participants older than 75 years suffered from a sharp decline in HRQoL; the participants in Shanghai and Tibet provinces reported lower utility and VAS scores and more health problems. Those who were younger, with better socioeconomic status and healthier lifestyles, and without diseases tended to report higher utility and VAS scores and fewer health problems. CONCLUSIONS: This study derived the 5L population norms for China based on a representative population sample.


Asunto(s)
Estado de Salud , Encuestas Epidemiológicas , Calidad de Vida , Humanos , Masculino , Femenino , China , Persona de Mediana Edad , Adulto , Anciano , Adolescente , Adulto Joven , Niño , Factores Socioeconómicos , Encuestas y Cuestionarios , Factores de Edad , Factores Sexuales , Valores de Referencia , Modelos Logísticos
13.
Mol Cell Probes ; 75: 101958, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38518900

RESUMEN

OBJECTIVE: The effects of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-exos) on serum metabolites and intestinal microbiota in rats after liver trauma were discussed. METHODS: Adult Wistar Albino rats were assigned into control, model (liver trauma), MSCs, and MSC-exos groups (n = 6). The study examined changes in the inflammatory environment in liver tissues were analyzed by histological examination and analysis of macrophage phenotypes. Alterations in serum metabolites were determined by untargeted metabonomics, and gut microbiota composition was characterized by 16S rDNA sequencing. Correlations between specific gut microbiota, metabolites, and inflammatory response were calculated using Spearman correlation analysis. RESULTS: Rats with liver trauma after MSCs and MSC-exos treatment exhibited attenuated inflammatory infiltration and necrosis in liver tissues. MSCs and MSC-exos treatment reduced the proportion of M1 macrophages, accompanied by a decrease in inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) levels. Furthermore, MSCs and MSC-exos treatment expanded the proportion of M2 macrophages, accompanied by an increase in arginase-1 (Arg-1) and interleukin-10 (IL-10) levels. The beneficial effects of MSC-exo treatment on rats with liver trauma were superior to those of MSC treatment. The composition and abundance of the gut microbiota and metabolites were altered in pathological rats, whereas MSC and MSC-exo intervention partially restored specific gut microbiota and metabolite alterations. At the phylum level, alterations in Bacteroidota, Proteobacteria, and Verrucomicrobiota were observed after MSC and MSC-exo intervention. At the genus level, Intestinimonas, Alistipes, Aerococcus, Faecalibaculum, and Lachnospiraceae_ND3007_group were the main differential microbiota. 6-Methylnicotinamide, N-Methylnicotinamide, Glutathione, oxidized, ISOBUTYRATE, ASCORBATE, EICOSAPENTAENOATE, GLYCEROL 3-PHOSPHATE, and Ascorbate radical were selected as important differential metabolites. There was a clear correlation between Ascorbate, Intestinimonas/Faecalibaculum and inflammatory cytokines. CONCLUSION: MSC-exos promoted the repair of tissue damage in rats with liver trauma by regulating serum metabolites and intestinal microbiota, providing new insights into how MSC-exos reduced inflammation in rats with liver trauma.


Asunto(s)
Exosomas , Microbioma Gastrointestinal , Hígado , Células Madre Mesenquimatosas , Ratas Wistar , Animales , Exosomas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Hígado/metabolismo , Hígado/patología , Ratas , Masculino , Cicatrización de Heridas , Macrófagos/metabolismo , Inflamación/metabolismo
14.
BMC Gastroenterol ; 24(1): 238, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075408

RESUMEN

PURPOSE: To evaluate the impact of two different parameters (body position and distension medium) on the rectal sensory test in patients with functional constipation and provide data support for the development of standardized operating procedures in clinical practice. METHODS: Based on a single-center process of the rectal sensory test, 39 patients with functional constipation were recruited for rectal sensory test under different body positions and distension mediums. RESULTS: Among the items of the Constipation Scoring System, the score of frequency of bowel movements showed a negative correlation with the first constant sensation volume (r = -0.323, P = 0.045). Conversely, the score of painful evacuation effort showed a positive correlation with the desire to defecate volume (r = 0.343, P = 0.033). There was a statistically significant difference in the first constant sensation volume (when the distension medium was gas) measured in different body positions (left lateral position, sitting position, squatting position), and the data measured in the squatting position were significantly higher than those in left lateral position (P < 0.05). In terms of research on distension medium, it was found that the first constant sensation volume measured in the squatting position (when the distension medium was water) was significantly lower than that of gas (P < 0.05). CONCLUSION: For patients with functional constipation, there are differences in the results of rectal sensory tests between body positions and distension mediums. When conducting multicenter studies, it is necessary to unify the standard operating procedure (SOP) for operational details to ensure consistency and reliability of the test results.


Asunto(s)
Estreñimiento , Posicionamiento del Paciente , Recto , Humanos , Estreñimiento/fisiopatología , Estreñimiento/diagnóstico , Femenino , Recto/fisiopatología , Masculino , Adulto , Persona de Mediana Edad , Posicionamiento del Paciente/métodos , Defecación/fisiología , Sensación/fisiología , Anciano , Adulto Joven
15.
Environ Sci Technol ; 58(27): 12225-12236, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38885124

RESUMEN

Nanoscale zerovalent iron synthesized using borohydride (B-NZVI) has been widely applied in environmental remediation in recent decades. However, the contribution of boron in enhancing the inherent reactivity of B-NZVI and its effectiveness in removing hexavalent chromium [Cr(VI)] have not been well recognized and quantified. To the best of our knowledge, herein, a core-shell structure of B-NZVI featuring an Fe-B alloy shell beneath the iron oxide shell is demonstrated for the first time. Alloyed boron can reduce H+, contributing to more than 35.6% of H2 generation during acid digestion of B-NZVIs. In addition, alloyed B provides electrons for Fe3+ reduction during Cr(VI) removal, preventing in situ passivation of the reactive particle surface. Meanwhile, the amorphous oxide shell of B-NZVI exhibits an increased defect density, promoting the release of Fe2+ outside the shell to reduce Cr(VI), forming layer-structured precipitates and intense Fe-O bonds. Consequently, the surface-area-normalized capacity and surface reaction rate of B-NZVI are 6.5 and 6.9 times higher than those of crystalline NZVI, respectively. This study reveals the importance of alloyed B in Cr(VI) removal using B-NZVI and presents a comprehensive approach for investigating electron pathways and mechanisms involved in B-NZVIs for contaminant removal.


Asunto(s)
Borohidruros , Boro , Hierro , Hierro/química , Borohidruros/química , Boro/química , Cromo/química , Electrones , Aleaciones/química
16.
Environ Sci Technol ; 58(32): 14282-14292, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39083369

RESUMEN

Biodegradable flocculants are rarely used in waste activated sludge (WAS) fermentation. This study introduces an alginate-based biodegradable flocculant (ABF) to enhance both the dewatering and degradation of WAS during its fermentation. Alginate was identified in structural extracellular polymeric substances (St-EPS) of WAS, with alginate-producing bacteria comprising ∼4.2% of the total bacterial population in WAS. Owing to its larger floc size, higher contact angle, and lower free energy resulting from the Lewis acid-base interaction, the addition of the prepared ABF with a network structure significantly improved the dewaterability of WAS and reduced capillary suction time (CST) by 72%. The utilization of ABF by an enriched alginate-degrading consortium (ADC) resulted in a 35.5% increase in the WAS methane yield owing to its higher hydrolytic activity on both ABF and St-EPS. Additionally, after a 30 day fermentation, CST decreased by 62% owing to the enhanced degradation of St-EPS (74.4%) and lower viscosity in the WAS + ABF + ADC group. The genus Bacteroides, comprising 12% of ADC, used alginate lyase (EC 4.2.2.3) and pectate lyase (EC 4.2.2.2 and EC 4.2.2.9) to degrade alginate and polygalacturonate in St-EPS, respectively. Therefore, this study introduces a new flocculant and elucidates its dual roles in enhancing both the dewaterability and degradability of WAS. These advancements improve WAS fermentation, resulting in higher methane production and lower CSTs.


Asunto(s)
Alginatos , Fermentación , Floculación , Aguas del Alcantarillado , Anaerobiosis , Eliminación de Residuos Líquidos , Biodegradación Ambiental
17.
Environ Sci Technol ; 58(4): 1966-1975, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38153028

RESUMEN

Polysaccharides in extracellular polymeric substances (EPS) can form a hybrid matrix network with proteins, impeding waste-activated sludge (WAS) fermentation. Amino sugars, such as N-acetyl-d-glucosamine (GlcNAc) polymers and sialic acid, are the non-negligible components in the EPS of aerobic granules or biofilm. However, the occurrence of amino sugars in WAS and their degradation remains unclear. Thus, amino sugars (∼6.0%) in WAS were revealed, and the genera of Lactococcus and Zoogloea were identified for the first time. Chitin was used as the substrate to enrich a chitin-degrading consortium (CDC). The COD balances for methane production ranged from 83.3 and 95.1%. Chitin was gradually converted to oligosaccharides and GlcNAc after dosing with the extracellular enzyme. After doing enriched CDC in WAS, the final methane production markedly increased to 60.4 ± 0.6 mL, reflecting an increase of ∼62%. Four model substrates of amino sugars (GlcNAc and sialic acid) and polysaccharides (cellulose and dextran) could be used by CDC. Treponema (34.3%) was identified as the core bacterium via excreting chitinases (EC 3.2.1.14) and N-acetyl-glucosaminidases (EC 3.2.1.52), especially the genetic abundance of chitinases in CDC was 2.5 times higher than that of WAS. Thus, this study provides an elegant method for the utilization of amino sugar-enriched organics.


Asunto(s)
Quitinasas , Aguas del Alcantarillado , Amino Azúcares , Fermentación , Ácido N-Acetilneuramínico , Quitina/química , Quitina/metabolismo , Polisacáridos , Quitinasas/química , Quitinasas/metabolismo , Metano
18.
Bioorg Med Chem ; 100: 117631, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38330848

RESUMEN

Acute myeloid leukemia (AML) is the most common type of blood cancer and has been strongly correlated with the overexpression of Fms-like tyrosine kinase 3 (FLT3), a member of the class III receptor tyrosine kinase family. With the emergence of FLT3 internal tandem duplication alteration (ITD) and tyrosine kinase domain (TKD) mutations, the development of FLT3 small molecule inhibitors has become an effective medicinal chemistry strategy for AML. Herein, we have designed and synthesized two series of 1H-pyrrolo[2,3-b]pyridine derivatives CM1-CM24, as FLT3 inhibitors based on F14, which we previously reported, that can target the hydrophobic FLT3 back pocket. Among these derivates, CM5 showed significant inhibition of FLT3 and FLT3-ITD, with inhibitory percentages of 57.72 % and 53.77 % respectively at the concentration of 1 µΜ. Furthermore, CM5 demonstrated potent inhibition against FLT3-dependent human AML cell lines MOLM-13 and MV4-11 (both harboring FLT3-ITD mutant), with IC50 values of 0.75 µM and 0.64 µM respectively. In our cellular mechanistic studies, CM5 also effectively induces apoptosis by arresting cell cycle progression in the G0/G1 phase. In addition, the amide and urea linker function were discussed in detail based on computational simulations studies. CM5 will serve as a novel lead compound for further structural modification and development of FLT3 inhibitors specifically targeting AML with FLT3-ITD mutations.


Asunto(s)
Leucemia Mieloide Aguda , Tirosina Quinasa 3 Similar a fms , Humanos , Apoptosis , Línea Celular Tumoral , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Piridinas/farmacología
19.
Proc Natl Acad Sci U S A ; 118(14)2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33790019

RESUMEN

Nonlinear mechanics of solids is an exciting field that encompasses both beautiful mathematics, such as the emergence of instabilities and the formation of complex patterns, as well as multiple applications. Two-dimensional crystals and van der Waals (vdW) heterostructures allow revisiting this field on the atomic level, allowing much finer control over the parameters and offering atomistic interpretation of experimental observations. In this work, we consider the formation of instabilities consisting of radially oriented wrinkles around mono- and few-layer "bubbles" in two-dimensional vdW heterostructures. Interestingly, the shape and wavelength of the wrinkles depend not only on the thickness of the two-dimensional crystal forming the bubble, but also on the atomistic structure of the interface between the bubble and the substrate, which can be controlled by their relative orientation. We argue that the periodic nature of these patterns emanates from an energetic balance between the resistance of the top membrane to bending, which favors large wavelength of wrinkles, and the membrane-substrate vdW attraction, which favors small wrinkle amplitude. Employing the classical "Winkler foundation" model of elasticity theory, we show that the number of radial wrinkles conveys a valuable relationship between the bending rigidity of the top membrane and the strength of the vdW interaction. Armed with this relationship, we use our data to demonstrate a nontrivial dependence of the bending rigidity on the number of layers in the top membrane, which shows two different regimes driven by slippage between the layers, and a high sensitivity of the vdW force to the alignment between the substrate and the membrane.

20.
J Basic Microbiol ; 64(1): 32-41, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37699751

RESUMEN

The morphological and structural differences of different types of chlamydospore of Arthrobotrys flagrans, a nematophagous fungus, were studied under light microscope and electron microscope to provide a reference for the biological control of parasitic nematodiasis. In this study, A. flagrans isolate F088 dormant chlamydospore and nondormant chlamydospore were selected as the research objects. The structural differences of these spores were observed by optical microscopy through lactol cotton blue, Trypan blue, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining. FunXite -1, 4',6-diamidino-2-phenylindole, and calcofluor white staining were used to observe the metabolic activity, cell wall, and nucleus differences of the two types of spores under fluorescence microscope. Ultrastructure of the two kinds of spores was observed using scanning electron microscope (SEM) and transmission electron microscope (TEM). Since lacto phenol cotton blue, trypan blue staining cannot distinguish dormant spores from dead spores, MTT assay was performed. Fluorescence microscopy observation showed that the cytoplasmic metabolic activity of nondormant spores was stronger than that of dormant spores. The nucleus of dormant spores was bright blue, and their fluorescence was stronger than that of nondormant spores. The cell wall of nondormant spores produced stronger yellow-green fluorescence than that of dormant spores. Ultrastructural observation showed that there were globular protuberances on the surface of the two types of spores but with no significant difference between them. The inner wall of dormant spore possesses a thick zona pellucida with high electron density which was significantly thicker than that of nondormant spores, and their cytoplasm is also changed. In this study, the microstructure characteristics of dormant and nondormant chlamydospores of A. flagrans fungi were preliminarily clarified, suggesting that the state of cell wall and intracellular materials were changed after spores entered to dormancy.


Asunto(s)
Ascomicetos , Azul de Tripano , Esporas Fúngicas , Heces/microbiología , Control Biológico de Vectores
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